Abstract LB-270: Exploration of TCGA generated DNA copy number data in ovarian cancer points to interesting proapaptotic gene for survival prediction

Abstract

Abstract Exploration of TCGA generated DNA copy number data in ovarian cancer points to interesting proapaptotic gene for survival prediction Using data generated by The Cancer Genome Atlas (TCGA) project, we investigated the use of copy number changes in prediction of both response to therapy as well as identification of possible prognostic survival bio-markers. The analysis was performed using an initial data set of 557 arrays (68 Affymetrix 6.0 and 489 Agilent 244K arrays). The raw data was processed using Nexus Copy Number version 5.1 software (BioDiscovery, El Segundo CA) and regions of copy number change were identified using the built-in FASST and SNP-FASST algorithms. As previously reported, using only the Agilent data set, we had identified a number of regions with statistically significant differences across between sample groups that responded to therapy as compared to those with progressive disease1. Performing gene enrichment analysis on these regions indicated a relationship with apoptosis. In our current study, we have also considered survival and have identified FAM105A located on the short arm of chromosome 5 as a possible component of Ovarian Cancer. A number of studies have identified the small 728Kb region between TRIO and ANKH gained in various cancers and hypothesized that these genes are possible oncognes2–3. Using Kaplan-Mier survival analysis, we have in fact been able to show that the FAM105A gene located between TRIO and ANKH is highly predictive of survival (p=0.00024) with the deletion causing a much poorer prognosis. This result was validated using the Affymetrix data on a different set of samples. Very little is known about this gene except the fact that using functional screening, it has demonstrated strong proapaptotic behavior which is in concordance with our findings here4. We are in the process of expanding the validation data set to several hundred samples. 2 Judith N Kloth, Jan Oosting, Tom van Wezel, Karoly Szuhai, Jeroen Knijnenburg, Arko Gorter, Gemma G Kenter, Gert Jan Fleuren, and Ekaterina S Jordanova, Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex genetic alterations in cervical cancer, BMC Genomics. 2007; 8: 53. Published online 2007 February 20. doi: 10.1186/1471–2164–8-53. 3 Coe BP, Henderson LJ, Garnis C, Tsao MS, Gazdar AF, Minna J, Lam S, Macaulay C, Lam WL., High-resolution chromosome arm 5p array CGH analysis of small cell lung carcinoma cell lines, Genes Chromosomes Cancer. 2005 Mar;42(3):308–13. 4 Otto Mannherz, Daniel Mertens, Meinhard Hahn, Peter Lichter, Functional screening for proapoptotic genes by reverse transfection cell array technology, Genomics, Volume 87, Issue 5, May 2006, Pages 665–672, ISSN 0888–7543, DOI: 10.1016/j.ygeno.2005.12.009. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-270. doi:10.1158/1538-7445.AM2011-LB-270